Patients with well-documented chronic non-A, non-B hepatitis are being evaluated to determine the long-term natural history of this common form of chronic liver disease. A cohort of such patients are available to evaluate experimental therapies for this disease. To date 12 patients with chronic non-A, non-B hepatitis have been treated with recombinant human alpha interferon for periods ranging from 4 to 15 months. Ten of the 12 patients have shown a dramatic decrease in serum aminotransferase levels during therapy, their levels falling from values 3 to 10 times the upper limit of the normal range to normal (7 patients) or near-normal (3 patients). Follow up liver biopsies have been obtained from nine patients, which demonstrates marked improvement in the hepatitis disease activity (a decrease in both inflammation and hepatocellular necrosis). The optimum dose appears to be 2 million units (mu) given three times per week. A prospective, randomized, placebo-controlled, double-blind trial of a six month course of human alpha interferon in patients with chronic non-A, non-B hepatitis is underway. Patients with chronic non A, non B hepatitis are evaluated in the Outpatient Clinic and then on the ward, where a percutaneous liver biopsy is obtained. Approximately 1 week later, therapy is commenced with either interferon 1 mu sc or placebo sc three times a week. After 6 months the treatment will be discontinued. Patients who received placebo will then be offered interferon therapy.